Fig. 6.

Effect of the number of Ca²⁺channels on release probability. A,I_Ca predicted by Hodgkin–Huxley Model for different AP waveforms. Trace 1, Physiological AP.Trace 2, Step AP to reduce peak channel open probability (p_open). Trace 3, Average I_Ca (used in uniformi_Ca mode) for 12 channel cluster (physiological AP); half-width of I_Ca = 383 μsec; p_open = 69%. Trace 4, Same as trace 3 but for step AP;p_open = 42%. Trace 5, Example of stochastic I_Ca (used in stochastic i_Ca mode) for cluster of 12 channels (physiological AP). Trace 6, Same astrace 5 but for step AP. B, Effects of the number of channels per cluster on apparent Hill coefficientm (see Property III for details). Solid line, m predicted by time-independent model.Squares, m predicted by time-dependent model with the stochastic i_Ca mode (for allN the vesicle locations are as described for the reference topography). Error bars indicate ± SEM after 400 Monte Carlo simulations for each data point. Open circles, Apparent Hill coefficient predicted by time-dependent model with the uniform i_Ca mode.C, Number and position of Ca²⁺channels in clusters of different N (1–100) used in the simulation. Grid indicates (5 nm)³ voxels on the membrane; the black circles indicate a voxel with a channel. The cluster with N = 100 channels is the same as the cluster with N = 1 channel except that the same voxel holds 100 channels instead of 1 (unrealistic channel density). Reaction volume, as well as location of readily releasable vesicles and of cluster centers (indicated by the black circle inN = 1 cluster) on AZs, is as in Figure7A. D, Coefficient of variation of the total Ca²⁺ influx through a cluster [time integral of I_Ca(t), 0–5 msec] as a function of the number of channels per cluster (physiological AP waveform).